Genetic Association of IFITM3 rs12252 Variant with Severe COVID-19 Outcomes in Syrian Patients

Abstract

Introduction: Following the COVID-19 pandemic, increasing attention has been directed toward host genetic factors that influence disease severity. The interferon-induced transmembrane protein 3 (IFITM3) plays a key role in restricting viral entry, and its rs12252 polymorphism has been linked to impaired antiviral defense and adverse clinical outcomes. Investigating rs12252 in the Syrian population may help clarify genetic determinants of COVID-19 progression.

Methodology: A cohort study was conducted in Syria, including 82 COVID-19 patients, who were clinically classified into two groups: severe (n = 41) and moderate (n = 41). Genomic DNA was extracted from peripheral blood samples, and genotyping of the IFITM3 rs12252 polymorphism was performed using MscI restriction enzyme digestion. Genotype distributions were analyzed to evaluate potential associations with disease severity.

Results: The frequency of the IFITM3 rs12252 C allele was higher in patients with severe COVID-19 (37.8%) compared to patients with moderate disease (29.3%). A statistically significant association was observed between the TC genotype (compared with TT and CC genotypes) and ICU admission (OR = 6.94; 95% CI: 1.48–32.54; p = 0.0033). After adjusting for age, the association remained significant (OR = 4.83; 95% CI: 0.93–25.09; p = 0.037).

Conclusions: These findings suggest that the IFITM3 rs12252 C allele is associated with severe COVID-19 outcomes in the Syrian cohort. Screening for this variant may assist in early risk stratification and support personalized management strategies, particularly in resource-limited settings.